Diphenyl derivatives and a process of preparing them



Patented Aug. 17, 1937 UNITED STAES PATENT OFFICE DIPHENYL DERIVATIVESAND A PROCESS OF PREPARING THEM Karl Zahn and Kurt Schimmelschmidt,Frankfort-on-the-Main, Germany, assignors to General Aniline Works,Inc., New York, N. Y., a corporation of Delaware No Drawing. ApplicationJune 14, 1932, Serial No. 617,260. In Germany June 24, 1931 7 Claims.

Our present invention relates to new diphenyl derivatives and to aprocess of preparing them; more particularly it relates to compounds ofthe following general formula:

OR wherein X stands for a radical of the benzene series, R. for alkyl oraralkyl and Y for hydrogen, a nitroor an amino-group.

We have found that the nitration of 2,5-dialkoxy-diphenyls or theirsubstitution products,

being unsubstituted in the 4-position, occurs in an easy way and in avery good yield with the formation of mononitro-2,5-dialkoxy-diphenylswhich may be converted into amino-2,5-dia1koxydiphenyls by reducing themin the usual manner, for example, by means of hydrogen in the presenceof a catalyzer, iron, zinc and tin in the presence of acids,aluminium-amalgam, sodium hydrosulfide (NaSI-I), etc. This result couldin 7 no way be foreseen; it had rather to be expected that, according tothe knowledge gained in the nitration of diphenyl (cf., for instance,Ind. and Eng. Chem. vol. 22, [1930], page 31; Journal of Chem. S003,London, 1926, page 1239), in an unsymmetrical diphenyl, in the simplestcase a 2,5- disubstituted diphenyl, the nitro-group would enter the 2-,4'-, 1- or G-position. Probably, the new compounds correspond with theconstitution of 4nitro-, and 1-amino-2,5-dialkoxy-diphenyls,respectively:

HaGO H CH3 OCH:

In an analogous manner there are obtained from diphenyls substituted in2,5-position by aralkyloxy-groups the 4-nitro 2,5 diaralkyloxy-diphenylsand the corresponding 4-amino-diphen- The ethers of2,5-dihydroxy-diphenyls, used as starting materials, may be prepared byreducing the phenyl-quinones obtainable in an easy Way according to thestatements in the U. S. Patent No. 1,735,432 (of. Borsche, Annalen derChemie, vol. 312 [1900], page 221) and etherifying in the usual mannerthe phenyl-hydroquinones thus obtained.

O OH

OCH:

is obtained:

214 parts of 2,5-dimethoxy-diphenyl (melting at 42 C., boiling at 180 C.under a pressure of mm. Hg) are triturated with 250 parts by volume ofglacial acetic acid; to this mixture moo OCH:

there are added, without cooling, 75 parts by volume of nitric acid ofspecific gravity 1.4. The

nitration takes place with excessive self-heating;

on cooling, the reaction mixture solidifies to a thick crystallinemagma. The nitro-compound is freed from the mother liquor by filteringwith suction and by subsequent washing with methanol. After drying, 230to 240 parts of a yellow product, melting at 101 C. to 103 C., areobtained. By recrystallizing the crude product from glacial acetic acid,yellow needles are obtained which melt at 102 C. to 103 0.; hence itfollows that the crude product is already pure and uniform. According tothe analysis a mononitro-dimethoxy--diphenyl has been obtained. (Contentof nitrogen; calculated 5.41, found 5.64). I The same product isobtainable by treating 2,5- diinethoxy-diphenyl in the ball mill with 3times its weight of nitric acid of specific gravity 1.2.

(2) According to this example 4-amino-2,5-dimethoxy-diphenyl of thefollowing formula:

OCHH is obtained.

In a horizontal autoclave provided with a stirrer there are treated withhydrogen gas, under pressure, 259 parts of 4-nitro-2,5-dimethoxy-di- 3Qphenyl and 1000 parts by volume of alcohol in the presence of a nickelcatalyzer, precipitated on pumice stone (i. e.,'2.5 to 5 grams of activenickel) The reduction occurs with excessive self-heating. When theabsorption of hydrogen is finished, the content of the autoclave isfreedfrom the catalyzer by filtering with suction while hot and thesolutionof the base obtained is caused to crystallize by cooling. Byconcentrating the mother liquor, further quantities of crystallizedproduct are obtained. 200 to 210 parts of a crude product in the form ofwhite leaflets, melting at 89 C., are obtained. The melting point of thebase cannot be raised by recrystallization: from which it follows thatthe base is pure.

The alcoholic solution of the reduction product may also be worked up insuch a manner that the alcohol is distilled off and the remaining baseis distilled in vacuo.

(3) By replacing in Example (1) 2,5-dimethoxy-diphenyl by 242 parts of2,5-diethoxyv-di phenyl (boiling at 175 C. to 190 C. under a pressure of.8 mm. Hg) 4-nitro-2,5-diethoxy-diphenyl of the melting point 92 C. isobtained. By reducing this nitro-compound, 4-amino-2,5-diethoxydiphenyl,melting at 72 C. to 73 C. is obtained.

(4) By replacing in Example (1) 2,5-dimethoxy-diphenyl by 244 parts of2,5,4-trimethoxydiphenyl (melting at 62 C. to 64 C.), 4nitro-2,5,4-trimethoxy-diphenyl, melting at 106 C., is

obtained. The catalytical reduction of this nitro compound yields4amino-2,5,4trimethoxy-diphenyl, melting at 125 C. to 126 C.

(5) 290'parts of 2,5-dimethoxy-terphenyl (2,5-dimethoxy-4'-phenyl-diphenyl), melting at 157 C. to 158 C., (obtainableby condensation of benzoquinone with para-diphenyl-diazonium-chloride soas to form diphenyl-benzoquinone, melting at 190 C. to 191 C., reductionto the hydroquinone, i. e. the 2,5-dihydroxy-terphenyl' of the meltingpoint 171 C. to 172 C., and methylation of this compound withdimethylsulfate in an alkaline solution) are triturated with 1500 partsby volume of glacial acetic acid; to this mixture there" are added 75parts by volume of nitric acid of specific gravity 1.4. Thereupon, thesus' pension is warmed until the Whole dissolves to a clear solution.After cooling, the precipitated nitro-compound is filtered with suction,covered with glacial acetic acid and Washed with water until neutral.There are obtained 280 to 290 parts of 4-nitr0-2,5-dimethoxy-terphenylin the (6) 298 parts of 2,5-dibutoxy-diphenyl (boiling at 200 C. under apressure of 10 mm. Hg) are introduced drop by drop, while stirring, at atemperature below 0 C. into 1000 parts by volume of nitric acid ofspecific gravity 1.4. nitro compound formed crystallizes from thereaction mixture. When the reaction is finished, the precipitation ofthe nitro compound is completed by introducing the whole into 2000 partsby volume of ice-Water and the new product is isolated by filtering withsuction and Washing with water until neutral; The product is freed fromsmall quantities of resin-like Thereby, the; even partly substancesadhering to it by making it into a.

paste with 400 parts by volume of ice-cold methyl-- alcohol, filteringitwith suction and washing it; with cold methyl alcohol. The4-nitro-2,5-dibutoxy-diphenyl obtained crystallizes from methylalcoholin the form of yellow needleswhich melt; at 41 C. to 42 C. By reducingthis nitro-compound, 4amino-2,5-dibutoxy-diphenyl is obtained, meltingat 52 C. to 53 C.

(7) 250 parts of I 2,5-dimethoXy-3'chlor0diphenyl (melting at 43 C. to44 C.) are dissolved in 500 parts by volume of glacial acetic acid. 75parts by volume of nitric acid of specific gravity 1.4are run into thissolution, while well cooling. The nitration'takes place at once withexcessive self-heating and the reaction mixture solidifies to acrystalline magma. The nitro-compound is freed from the mother liquor byfiltering with suction and washing with methanol. 250 parts of 4nitro-2,5-dimethoxy-3'-chlorodiphenyl are obtained in the form of yellowneedles which melt at 127 C. By reducing this nitro compound, 4-amino-2,5dimethoxy-3'-chloro-diphenyl, melting at 68 C. to 69 C. isobtained.

('8) 283 parts of 2,5-dimethoxy-3',5'-dichlorodiphenyl (melting at 104C. to 107 C.) are dissolved in 600 parts by volume of glacial aceticacid and, after the mixture has been allowed to cool, 60 parts by volumeof fuming nitric acid (of 96% strength) are gradually added thereto,while Well cooling. The nitro-compound separates at once in the form ofcrystals and is freed from the mother liquor by filtering with suctionand washing with methanol. 280 parts of 4-nitro-2,5-dimethoxy-3',5'-dichloro-diphenyl, melting at 149 C. to 150 C., areobtained. By reducing this nitro-compound, 4-amino-2,5-dimethoxy-3,5'-dichloro-diphenyl, which melts at 161 C. to 163 C., is obtained;

Parent material Nitro-compound Amino-compound 2,5 dimethoxy 4 v methyldigg eiyl, melting at 66 C. to

2,5 dimethoxy 2' methyl di-. pfih egyl, melting at 74 C. to-

2,5 dimethoxy -'2 chloro diphenyl, boiling at 180 C. underapressure of 8mm; Hg.

2,5 dimethoxy, 4 chloro di- 7 phenyl, melting at 63 C. to 64 0 2,5dimethoxy 4- benzoylamino-diphenyl, melting at 148 C. to 149 C.

2,5 dimethoxy 3,4 diohlorogplbenyl, melting at 58 C. to

2,5-dimethoxy-2,4-dichloro-diphenyl, boiling at 195 0. un der a pressureof 8 mm. Hg.

2,5-dibenzyloxy-diphenyl, melting at 98 0. to 100 0.

methyl-)diphenyl, boiling. at

' 167 C. under a pressure of 8 mm. Hg.

2, 5-dimethoxy-2 ,4 -dimethyl-diphenyl, boiling at 178 0. under apressure of 8 mm. Hg.

2,5,4 trimethoxy 2 chlorodiphenyl, boiling at 205 C.

under a pressure of 8 mm. Hg. 2,5,4 trimethoxy 3 chloro under a pressureof 8 mm. Hg.

2,5 dimethoxy 4 chloro 2 methyl-diphenyl, boiling at 190 C. under apressure of 8 mm. Hg.

2,5,2 trimethoxy 5 -methyl diphenyl, melting at 98 C. to 100 C to2,5-dibutoxy-3-chloro-diphenyl,

boiling at 220 C. under a pressure of 8 mm. Hg. 2,5 dimethoxy 3 methyldiphenyl, boiling at 170 C. under a pressure of 8 mm. Hg.

2,5 diethoxy 3 methyl diphenyl, boiling at 178 C. under a pressure of 8mm. Hg.

2,5,2 trimethoxy diphenyl, boiling at 192 C. to 193 C. under a pressureof 8 mm. Hg.

2,5 dimethoxy 3 methylsulfonyl-diphenyl, boiling at 260 C. under apressure of 8 mm. Hg.

2,5 dimethoxy 2,5 dichlorodiphenyl, boiling at 195 C. under a pressureof 8 mm. Hg.

2,5 dimethoxy 5' chloro 2- methyl-diphenyl, boiling at 185 C. under apressure of 8 mm. Hg.

4 nitro 2,5 dimethoxy 4- methyl-diphenyl, melting at 167 C.

{4 nitro 2,5 dimethoxy 2- .4 nitro 2,5 dirnethoxy 2,4-dichloro-diphenyl,melting at 125 C. to 127 C.

4 nitro 2,5 dibenzyloxy diphenyl, melting at 136 C. to 138 C 4 nitro 2,5dimethoxy-3-(w-trifluormethyl-)diphenyl, melting at 139 C. to 140 C. j

4-nitro-2,5rdimethoxy-2,4-dimethyl-diphenyl, melting at 126 C. to 127'0.

4 nitro 2,5,4 trimethoxy 2- chlorodiphenyl, melting at 132 C. to 133 C.

4- nitro 2,5,4 trimethoxy 3 chlorodiphenyl, melting at 127 C. to 128 C.

4-nitro-2,5dimethoxy-4-chloro- 2-methyl-diphenyl, melting at 150 C. to151 0.

4 nitro 2,5,2 trimethoxy 5 methyl-diphenyl, melting at 112 C. to 113 C.

4-nitro-2,5-dimethoxy-2 ,4 ,5 -trichloro-diphenyl, melting at 156 C. to157 C.

4-nitro-2,5-dimethoxy-3,4,5-trichloro-diphenyl, melting at 190 C. to 191C.

4 nitro 2,5,2 ,5 tetramethoxy- 4-chloro-diphenyl, melting at 187 C. to190 C.

4 nitro 2,5,2,4 tetramethoxy- 5chloro-diphenyl, melting at 192 to 193 C.

4-nitro-2,5-dibutoxy-3 -chlorodiphenyl, melting at 60 C.

4 nitro 2,5 dimethoxy 3 meiiyl-diphenyl, melting at 114 4 nitro 2,5diethoxy-3-methto 76 C.

4 nitro 2,5,2 trimethoxy diphengl, melting at 114 C. to 116 4 nitro- 2,5dimethoxy 3- methyl sulionyl diphenyl, melting at 192 C,

4 nitro 2,5 dimethoxy 2,5-

dichloro-diphenyl, melting at 147 C. to 148 C.

4 nitro 2,5 dimethoxy 5- chloro 2 methyl diphenyl, melting at 110 C. to111 C.

methyl-diphenyl, melting at O to 87 0.

melting at 1 yl-diphenyl, melting at 75 C.

4 amino 2,5 dimethoxy 4- 103 C. 4 amino 2,5 dimethoxy 2-methyl-diphenyl, melting at amine- 2,5 dimethoxy 2 chlo'rodiphenyl;melting at 131 C. to 132 C.

4 amino 2,5 dimethoxy 4- chloro-diphenyl, melting at 101 C. to 102 C.

4 amino 2,5 dimethoxy 4- ;3 '.benzoyl-amino-diphenyl, melting at 150 C.

4 amino 2,5 dimethoxy 3,4-

dichloro-diphenyl, melting at 113 C4amino-2,5-dimethoxy-2,4-dichloro-diphenyl, melting at 100C 4 amino 2,5dibenzyloxy diphenyl, melting at 117 C. to 119 0 i 4- amino -2,5dimethoxy -2 ,4 -dimethyl-diphenyl melting at 99 0. to 100 C.

4 amino 2,5,4 trimethoxy 2- chloro diphenyl, melting at 112 C. to 113 C.

4 amino 2,5,4 trimethoxy 3 chloro diphenyl, melting at 101 C. to 103 C.

4-amino-2,5-dimethoxy-4-chlorofiigleghyl-diphenw, melting at 4 amino2,5,2 trimethoxy 5 methyl-diphenyl, melting at 107 C. to 108 0.

4-amino-2,5-dimethoxy-2,4,5-trichloro-diphenyl, melting at 126 C. to 127C.

4-amino-2,5-dimethoxy-3,4,5-trichloro-diphenyl, melting at 175 C. to 176C.

4 amino 2,5,2 ,5 tetramethoxy- 4-chloro-diphenyl, melting at 175 C. to179 0.

4 amino 2,5,2,4 tetramethoxy- 5-chloro-diphenyl, melting at 148 C. to149 C.

4- amino -2,5 dibutoxy 3 chlorodlphenyl, fluid, forming a wellorystallizing chlorohydrate.

4-amino-2,5-dimethoxy 3 methyl'- diphenyl, fluid, forming a wellcrystallizing chlorohydrate.

4-am' 0 2,5 diethoxy 3' methyl diphenyl, fluid, forming a wellcrystallizing chlorohydrate.

4 amino 2,5,2 trimethoxy diphenyl, fluid, forming a well crystallizingchlorohydrate.

4 amino 2,5 dimethoxy 3- methyl sulfonyl diphenyl, fluid, forming a wellcrystallizing chlorohydrate.

4 amino 2,5 dimethoxy 2,5- dichloro-diphenyl, fluid, forming a wellcrystallizing chlorohydrate.

4 amino 2,5 dimethoxy 5- chloro 2 methyl diphenyl, fluid forming a wellcrystallizing chlorohydrate.

We claim:

1. The process which comprises nitrating methyl'-phenyl ,-and R foraradical-ofthe group consisting of benzyl and alkyl of the loweraliphatic series, and reducing the 4-nitro-diphenyl compounds obtainedto the corresponding diphenyl compounds of the following generalformula:

dimethoxy-diphenyl of the following formula:

wherein X stands for a radical of the group conand omega-trifiuoro-4-amino-diphenyl compounds.

2. The process which comp-rises nitrating 2,5-

OCH:

and reducing the 4-nitro-2,5-dimethoxy-diphenyl obtained to thecorresponding 4-amino-2,5- dimethoxy-diphenyl.

3. The compounds of the followingzgeneral formula:

OCHa

crystallizing from alcohol in the form of colorless leaflets of themelting point 89 C.

5. The compound of the following I formula:

OOH:

melting at C. to 126 C.

6. The process which comprises nitrating diphenyl compounds of thefollowing general formula: I t

OR I

wherein X stands for a radical of the benzene series and R for a radicalof the group consisting of benzyl and alkyl of the lower aliphaticseries, and reducing the -nitro-diphenyl compounds obtained to thecorresponding 4-amino-diphenyl compounds. 7. The compounds of thefollowing general formu1a: n.

wherein X stands for a radical of the benzene series, R for a radical ofthe group consisting of benzyl and alkyl of the lower aliphatic series,and Y for a member of. the group consisting of nitro and amino.

KARL ZAHN. KURT SCI-HlVIMELSCI-IIVIIDT.

